To determine the effect of plasma growth hormone (GH) on skeletal muscle function, we measured the free Ca²⁺ concentration-tension relationship of slow-twitch (soleus) and fast-twitch (peroneus longus) muscles isolated from rats undergoing acromegaly in response to implanted, GH-secreting tumors. Muscles from adult (9 mo) and aged rats (24 mo) were studied after the tumor-bearing rats weighed over 50% more than their age-matched controls. Ca²⁺-activated isometric tension was recorded from skinned muscle fibers. For soleus muscles, the free Ca²⁺ concentration producing 50% of maximal tension ([Ca²⁺]₅₀) was 2.0 µM for rats with tumors and 3.4-3.6 µM for controls. For peroneus longus fibers, [Ca²⁺]₅₀ shifted from 6.1-6.7 µM in controls to 3.5 µM after tumors were introduced into either adult or aged rats. Soleus muscle fibers from neonatal rats (14 days) were less sensitive to Ca²⁺ than those isolated from adult rats, having a [Ca²⁺]₅₀ of 7.3 µM. The Ca²⁺ sensitivity of peroneus longus fibers did not change with age. We conclude that significant increases in myofibrillar Ca²⁺ sensitivity occur in skeletal muscles undergoing rapid growth induced by GH-secreting tumors.